We have been conducting a molecular genetic investigation of crystallin abnormalities present in the Philly mouse lens. The Philly mouse develops dominantly inherited cataracts beginning approximately 30 days after birth, at which time a generalized decrease of all crystallins is also observed. A specific deficiency of a 27,000 dalton (27K) Beta-crystallin polypeptide and its functional mRNA was demonstrated in the pre-cataractous 10-day-old Philly mouse lens. Total RNAs and polyadenylated mRNAs were isolated from 20 to 30-day-old normal and Philly mouse lenses and analyzed by in vitro translation and Northern blot hybridization. There was no difference in the translational efficiency of the normal and Philly total RNA's, but a marked decrease in the translational efficiency of the Philly mRNAs compared to the normal mRNAs was noted. A specific, severe decrease in the translation of the 27K Beta-crystallin polypeptide was observed. The hybridization of murine Alpha, Beta, and Gamma-crystallin cDNA probes to the Northern blots of total RNAs and mRNAs from the normal and Philly lens demonstrated no difference in the levels of these crystallin RNA sequences in the total RNA populations, but a significant decrease in all of these crystallin mRNAs was present in the Philly mRNAs compared to the normal mRNAs. A marked deficiency in the level of the 23,000 dalton (23K) Beta-crystallin mRNA was observed. The hybridization of other murine Beta-crystallin cDNA probes to the mRNA Northern blots indicated that the 23K Beta-crystallin mRNA was most severely deficient in the Philly lens. A comparison of the in vitro translation products of the normal and Philly mRNAs with the hybrid selected translation products of the 23K Beta-crystallin cDNA suggested that the 23K Beta-crystallin, for which the cDNA and the gene have been isolated and studied, may be identical to the 27K Beta-crystallin polypeptide which is severely deficient in the Philly lens.